Priyansha Choubey1, Mohit Kwatra1, Surya Narayan Pandey1, Dinesh Kumar1, Durgesh Kumar Dwivedi1, Prabha Rajput1, Abhishek Mishra2, Mangala Lahkar3, Ashok Jangra4,5. 1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, India. 2. Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. 3. Department of Pharmacology, Gauhati Medical College, Guwahati, Assam, India. 4. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, India. ashok.jangra@kiet.edu. 5. Department of Pharmacology, KIET School of Pharmacy, KIET Group of Institutions, Ghaziabad, Uttar Pradesh, India. ashok.jangra@kiet.edu.
Abstract
BACKGROUND: Fisetin, a plant active polyphenol, is well known for its antioxidant and free radical scavenging activities. The present study was designed to explore the detailed molecular mechanism underlying its neuroprotective effects. METHODS: The young male mice were either administered a single dose of lipopolysaccharide (0.83 mg/kg) or subjected to restraint stress (6 h per day for 28 days) to induce behavioral deficits in different groups. Fisetin (15 mg/kg) was orally administered for the last 14 days of the study. RESULTS: Lipopolysaccharide (LPS) as well as restraint stress (RS) exposure caused behavioral alterations (anxiety and depressive-like behavior). Gene expression analysis showed upregulation of nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and indoleamine 2,3-dioxygenase (IDO)-1 gene expression along with downregulation of Nrf-2 (nuclear factor erythroid 2-related factor 2), HO-1 (heme oxygenase-1), and ChAT (choline acetyltransferase) gene expression level in RS and RS+LPS groups. Fisetin administration significantly ameliorated behavioral and neurochemical deficits in LPS, RS, and RS+LPS groups. CONCLUSION: These findings clearly indicated that fisetin administration improved behavioral functions and suppressed the NF-κB and IDO-1 (indoleamine 2,3-dioxygenase) activation along with their antioxidant effect, suggesting fisetin as an intriguing nutraceutical for the management of inflammation-associated neurological disorders.
BACKGROUND:Fisetin, a plant active polyphenol, is well known for its antioxidant and free radical scavenging activities. The present study was designed to explore the detailed molecular mechanism underlying its neuroprotective effects. METHODS: The young male mice were either administered a single dose of lipopolysaccharide (0.83 mg/kg) or subjected to restraint stress (6 h per day for 28 days) to induce behavioral deficits in different groups. Fisetin (15 mg/kg) was orally administered for the last 14 days of the study. RESULTS:Lipopolysaccharide (LPS) as well as restraint stress (RS) exposure caused behavioral alterations (anxiety and depressive-like behavior). Gene expression analysis showed upregulation of nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and indoleamine 2,3-dioxygenase (IDO)-1 gene expression along with downregulation of Nrf-2 (nuclear factor erythroid 2-related factor 2), HO-1 (heme oxygenase-1), and ChAT (choline acetyltransferase) gene expression level in RS and RS+LPS groups. Fisetin administration significantly ameliorated behavioral and neurochemical deficits in LPS, RS, and RS+LPS groups. CONCLUSION: These findings clearly indicated that fisetin administration improved behavioral functions and suppressed the NF-κB and IDO-1 (indoleamine 2,3-dioxygenase) activation along with their antioxidant effect, suggesting fisetin as an intriguing nutraceutical for the management of inflammation-associated neurological disorders.
Authors: Hyeon Joo Ham; Yong Sun Lee; Hee Pom Lee; Young Wan Ham; Jaesuk Yun; Sang Bae Han; Jin Tae Hong Journal: Front Cell Neurosci Date: 2022-03-07 Impact factor: 5.505